rs890293

Positions:

• chr1-59926822-C-A

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 1P and 9B. PP5 BP4 BA1

The XM_047447499.1(CYP2J2):​c.-99-10722G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0709 in 1,366,918 control chromosomes in the GnomAD database, including 3,774 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in Lovd as Pathogenic (no stars).

• Frequency:
  • Genomes: 𝑓 0.084 (641 hom., cov: 32)
  • Exomes 𝑓: 0.069 (3133 hom.)
• Consequence: CYP2J2 XM_047447499.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.19

Genes affected

CYP2J2 (HGNC:2634): (cytochrome P450 family 2 subfamily J member 2) This gene encodes a member of the cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are monooxygenases which catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids. This protein localizes to the endoplasmic reticulum and is thought to be the predominant enzyme responsible for epoxidation of endogenous arachidonic acid in cardiac tissue. Multiple transcript variants have been found for this gene. [provided by RefSeq, Jan 2016]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• PP5: Variant 1-59926822-C-A is Pathogenic according to our data. Variant chr1-59926822-C-A is described in Lovd as [Pathogenic].
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7). . Strength limited to SUPPORTING due to the PP5.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.139 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYP2J2	XM_047447499.1	c.-99-10722G>T		intron_variant			XP_047303455.1
CYP2J2	NM_000775.4			upstream_gene_variant		ENST00000371204.4	NP_000766.2
CYP2J2	NR_134981.2			upstream_gene_variant
CYP2J2	NR_134982.2			upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CYP2J2	ENST00000371204.4			upstream_gene_variant		1	NM_000775.4	ENSP00000360247	P1

Frequencies

GnomAD3 genomes AF: 0.0844 AC: 12846 AN: 152160 Hom.: 641 Cov.: 32

Gnomad AFR AF: 0.142

Gnomad AMI AF: 0.0143

Gnomad AMR AF: 0.0423

Gnomad ASJ AF: 0.0544

Gnomad EAS AF: 0.0443

Gnomad SAS AF: 0.0707

Gnomad FIN AF: 0.0551

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.0701

Gnomad OTH AF: 0.0731

GnomAD4 exome AF: 0.0692 AC: 84067 AN: 1214640 Hom.: 3133 Cov.: 17 AF XY: 0.0689 AC XY: 41642 AN XY: 604308

Gnomad4 AFR exome AF: 0.140

Gnomad4 AMR exome AF: 0.0307

Gnomad4 ASJ exome AF: 0.0554

Gnomad4 EAS exome AF: 0.0468

Gnomad4 SAS exome AF: 0.0620

Gnomad4 FIN exome AF: 0.0609

Gnomad4 NFE exome AF: 0.0704

Gnomad4 OTH exome AF: 0.0750

GnomAD4 genome AF: 0.0844 AC: 12850 AN: 152278 Hom.: 641 Cov.: 32 AF XY: 0.0819 AC XY: 6099 AN XY: 74472

Gnomad4 AFR AF: 0.142

Gnomad4 AMR AF: 0.0423

Gnomad4 ASJ AF: 0.0544

Gnomad4 EAS AF: 0.0440

Gnomad4 SAS AF: 0.0703

Gnomad4 FIN AF: 0.0551

Gnomad4 NFE AF: 0.0701

Gnomad4 OTH AF: 0.0723

Alfa AF: 0.0729 Hom.: 69

Bravo AF: 0.0849

Asia WGS AF: 0.0640 AC: 220 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	6.3
DANN	Benign	0.81

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs890293; hg19: chr1-60392494;